To the Editors:
The role of gastro-oesophageal reflux in idiopathic pulmonary fibrosis (IPF) has been given little consideration in the literature, and Raghu et al. 1 have made a significant contribution in this regard. However, if we examine their data in terms of attributable risk, the potential clinical impact of these findings becomes even clearer.
Several other reports have suggested a possible link between gastro-oesophageal reflux and IPF. A case–control study from 1976 determined the prevalence of reflux to be higher in 48 patients with IPF than in 270 age-matched controls with fibrosis of other aetiologies 2. Tobin et al. 3 previously published a smaller case–control study which identified that 16 out of 17 (94%) patients with IPF compared with four out of eight (50%) patients with interstitial lung disease due to other causes had abnormal acid exposure in the oesophagus. In 2005, Patti et al. 4 determined the prevalence of gastro-oesophageal reflux in IPF patients to be 66%, with a third of those patients having no reflux symptoms.
In the current study, 46 patients with IPF not currently receiving proton pump inhibitor (PPI) therapy were compared with 133 asthmatics also not receiving PPI therapy. All patients were subjected to 24-h pH-probe testing. The prevalence of abnormal acid exposure was 87 and 68% in IPF patients and asthmatics, respectively (statistically significant, p = 0.014). Thus, the odds of having IPF in those with abnormal acid exposure as compared to those without (odds ratio) is 3.19. The attributable risk percentage (ARP) calculated based on table 1⇓, which was constructed using data from the study by Raghu et al. 1, is 68.6%. If we assume a causal relationship between reflux and IPF, then simply stated the ARP means that 68.6% of the cases of IPF in patients with abnormal acid exposure would not have occurred in the absence of exposure. The population ARP is 49.8%, which means that in the population of patients studied, almost half of IPF cases identified would not have occurred in the absence of abnormal acid exposure.
Frequency of gastro-oesophageal reflux in patients with IPF and asthma
Unfortunately, the data presented by Raghu et al. 1 also suggest that only 47% of patients with abnormal acid exposure experienced gastrointestinal symptoms, meaning that symptom-targeted therapy may not be effective. Given the relatively low cost of proton pump inhibitor therapy and low side-effect profile compared with other available therapies for idiopathic pulmonary fibrosis, these data suggest that at the very least treatment with a proton pump inhibitor should be strongly considered in patients with idiopathic pulmonary fibrosis until better data are available. The data presented by Raghu et al. 1 also showed that 12 out of 19 patients on proton pump inhibitors still had abnormal results from pH-probe studies. More research needs to be carried out regarding the association between reflux and idiopathic pulmonary fibrosis to determine whether even more aggressive therapies should be considered, should treatment with proton pump inhibitors fail to adequately treat reflux.
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